State of the art and the dark side of amyotrophic lateral sclerosis

• 作者: Antonio Musarò
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: Amyotrophic lateral SCLEROSIS NEURODEGENERATIVE disease Muscle WASTING Oxidative stress EXCITOTOXICITY Protein aggregation Mitochondrial DYSFUNCTION INSULIN-LIKE growth factor 1
• 年，卷（期）: 2010,（5）
• 页码范围: 62-68
• 页数: 7页
• 分类号: R744

摘要

Amyotrophic lateral sclerosis(ALS) is a disorder that involves the degeneration of motor neurons,muscle atrophy,and paralysis.In a few familiar forms of ALS,mutations in the superoxide dismutase-1(SOD1) gene have been held responsible for the degeneration of motor neurons.Nevertheless,after the discovery of the SOD1 mutations no consensus has emerged as to which cells,tissues and pathways are primarily implicated in the pathogenic events that lead to ALS.Ubiquitous overexpression of mutant SOD1 in transgenic animals recapitulates the pathological features of ALS.However,the toxicity of mutant SOD1 is not necessarily limited to the central nervous system.Views about ALS pathogenesis are now enriched by the recent discovery of mutations in a pair of DNA/RNA-binding proteins called TDP-43 and FUS/TLS as causes of familial and sporadic forms of ALS.Although the steps that lead to the pathological state are well defined,several fundamental issues are still controversial:are the motor neurons the first direct targets of ALS;and what is the contribution of non-neuronal cells,if any,to the pathogenesis of ALS?The state of the art of ALS pathogenesis and the open questions are discussed in this review.